As in previous years, an integrated approach continues to be the major thrust of this project. A major focus has been upon the development of an improved technique for measuring mean retinal circulation time by means of fluorescein retinography. The baseline protocol for the performance of the fluorescein angiogram has been crystalized. The film development techniques have been rigorously standardized for constant reproducibility. An automatic scanning microdensitometric system has been under development and improvement in collaboration with a commerical company (Information Design, Bedford, Massachusetts). A computerized format for the rapid and simple computation of the retinal circulation times has been completed. Currently undergoing clinical trials in this laboratory is a prototype automatic focusing Fundus camera. This device should reduce both patient and operator variables which are apparent under the best of conditions in the performance of fluorescein retinography. Utilizing these new improvements for the optimization of the fluorescein retinogram and the calculation of the retinal circulation time, a prospective study of retinal blood flow will be continued with a heavy emphasis upon genetic prediabetic populations, mild-diabetic,and severe juvenile-onset, insulin-requiring diabetic patients. Relationships will be sought between the circulation time and metabolic factors, such as the degree of carbohydrate intolerance, the magnitude of the serum insulin and growth hormone responses during a variety of stimulation tests, and plasma lipids (cholesterol and triglyceride) in the normal, prediabetic, and mild-diabetic groups. In the overt diabetic groups, particularly the juvenile-onset type, annual fluorescein retinograms will be obtained and correlated to the degree of control of blood sugar, serum lipids and the clinical onset of other complications, particularly nephropathy. Bibliographic references: T.T., and Gleason, R.E.: Endogenous and Exogenous Insulin Responses in Patients with Cystic Fibrosis. Pediatrics 55:75-82, 1975. Ganda, O.P., Kahn, C.B., Soeldner, J.S., and Gleason, R.E.: Dynamics of Tolbutamide, Glucose, and Insulin Interrelationships Following Varying Doses of Intravenous Tolbutamide in Normal Subjects. Diabetes 24:354-361, 1975.